Absorbed Dose Estimation of 177Lu-DOTATOC in Adenocarcinoma Breast Cancer Bearing Mice
In this study, the absorbed dose of human organs after injection of 177Lu-DOTATOC was studied based on the biodistribution of the complex in adenocarcinoma breast cancer bearing mice. For this purpose, the biodistribution of the radiolabelled complex was studied and compartmental modeling was applied to calculate the absorbed dose with high precision. As expected, 177Lu-DOTATOC illustrated a notable specific uptake in tumor and pancreas, organs with high level of somatostatin receptor on their surface and the effectiveness of the radio-conjugate for targeting of the breast adenocarcinoma tumors was indicated. The elicited results of modeling were the exponential equations, and those are utilized for obtaining the cumulated activity data by taking their integral. The results also exemplified that non-target absorbed-doses such as the liver, spleen and pancreas were approximately 0.008, 0.004, and 0.039, respectively. While these values were so much lower than target (tumor) absorbed-dose, it seems due to this low toxicity, this complex is a good agent for therapy.
[1] M. Sandström , U. Garske-Román , D. Granberg , et al. “Individualized dosimetry of kidney and bone marrow in patients undergoing 177Lu-DOTA-Octreotate Treatment” J Nucl Med, vol.54, pp. 33-41, 2013.
[2] S. Pauwels , R Barone , S. Walrand ,et al. “Practical Dosimetry of Peptide Receptor Radionuclide Therapy with 90Y-Labeled Somatostatin Analogs” J Nucl Med, vol.46, pp. 92-98, 2005.
[3] http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-breast-cancer-types
[4] T. K. Nayak, J. P. Norenberg, T. L. Anderson, et al. “Somatostatin-receptor-targeted a-emitting 213Bi is therapeutically more effective than beta(-)-emitting 177Lu in human pancreatic adenocarcinoma cells” Nucl Med Biol, vol. 34, pp. 185-193, 2007.
[5] L. Bodei , J. Mueller-Brand , R. P. Baum , et al. “The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours” Eur J Nucl Med Mol Imaging, vol. 40, pp.800-816, 2013.
[6] M.Cremonesi, M. Ferrari, S. Zoboli, et al. “Biokinetics and dosimetry in patients administered with 111In-DOTA-Tyr3-octreotide: implications for internal radiotherapy with 90Y-DOTATOC” Eur.J.Nucl.Med.Mol. Imaging, vol. 26, pp. 877–886, 1999.
[7] S. Koukouraki, L. G. Strauss, V. Georgoulias , et al. “Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy.” Eur J Nucl Med Mol Imaging, vol. 33, pp. 460–466, 2006.
[8] E. Ilan, M. Sandström , C. Wassberg, et al. “Dose Response of Pancreatic Neuroendocrine Tumors Treated with Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE” J Nucl Med, vol. 56, pp. 177-182, 2015.
[9] B. L. R. Kam, J. J. M. Teunissen, E. P. Krenning, et al. “Lutetium-labelled peptides for therapy of neuroendocrine tumours” Eur J Nucl Med Mol Imaging, vol. 39, pp. 103-112, 2012.
[10] A. Romer, D. Seiler, N. Marincek, et al. ”Somatostatin-based radiopeptide therapy with (177Lu-DOTA)-TOC versus (90Y-DOTA)-TOC in neuroendocrine tumours” Eur J Nucl Med Mol Imaging, vol. 41, pp. 214-222, 2014.
[11] M. Cremonesi, M. Ferrari, L. Bodei, et al. “Dosimetry in Peptide Radionuclide Receptor Therapy: A Review” J Nucl Med, vol. 47, pp. 1467-1475, 2006.
[12] J. A. Jacquez, Compartmental analysis in biology and medicine. Amsterdam, Holland: Elsevier/North, 1972.
[13] D. Anderson. Compartmental modeling and tracer kinetics. Springer-Verlag: Berlin, 1983.
[14] J. Robertson. Compartmental distribution of radiotracers. Boca Raton, FL: CRC Press, 1983.
[15] H. Yousefnia, M. Mousavi-Daramoroudi, S. Zolghadri and F. Abbasi-Davani, “Preparation and biodistribution assessment of low specific activity 177Lu-DOTATOC for optimization studies.” Iran J Nucl Med, vol. 24, pp. 85-91, 2016.
[16] P. E. Valk, D. L. Bailey, D. W. Townsend, M. N. Maisey, Positron Emission Tomography: Basic Science and Clinical Practice. Springer-Verlag: London, 2003, pp. 147–179.
[17] M. G. Stabin and J. A. Siegel, “Physical Models and Dose Factors for Use in Internal Dose Assessment.” Health Phys, vol. 85, pp. 294-310, 2003.
[18] M. G. Stabin, R.B. Sparks, E. Crowe, “OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine.” J Nucl Med, vol. 46, pp. 1023–1027, 2005.
[1] M. Sandström , U. Garske-Román , D. Granberg , et al. “Individualized dosimetry of kidney and bone marrow in patients undergoing 177Lu-DOTA-Octreotate Treatment” J Nucl Med, vol.54, pp. 33-41, 2013.
[2] S. Pauwels , R Barone , S. Walrand ,et al. “Practical Dosimetry of Peptide Receptor Radionuclide Therapy with 90Y-Labeled Somatostatin Analogs” J Nucl Med, vol.46, pp. 92-98, 2005.
[3] http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-breast-cancer-types
[4] T. K. Nayak, J. P. Norenberg, T. L. Anderson, et al. “Somatostatin-receptor-targeted a-emitting 213Bi is therapeutically more effective than beta(-)-emitting 177Lu in human pancreatic adenocarcinoma cells” Nucl Med Biol, vol. 34, pp. 185-193, 2007.
[5] L. Bodei , J. Mueller-Brand , R. P. Baum , et al. “The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours” Eur J Nucl Med Mol Imaging, vol. 40, pp.800-816, 2013.
[6] M.Cremonesi, M. Ferrari, S. Zoboli, et al. “Biokinetics and dosimetry in patients administered with 111In-DOTA-Tyr3-octreotide: implications for internal radiotherapy with 90Y-DOTATOC” Eur.J.Nucl.Med.Mol. Imaging, vol. 26, pp. 877–886, 1999.
[7] S. Koukouraki, L. G. Strauss, V. Georgoulias , et al. “Evaluation of the pharmacokinetics of 68Ga-DOTATOC in patients with metastatic neuroendocrine tumours scheduled for 90Y-DOTATOC therapy.” Eur J Nucl Med Mol Imaging, vol. 33, pp. 460–466, 2006.
[8] E. Ilan, M. Sandström , C. Wassberg, et al. “Dose Response of Pancreatic Neuroendocrine Tumors Treated with Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE” J Nucl Med, vol. 56, pp. 177-182, 2015.
[9] B. L. R. Kam, J. J. M. Teunissen, E. P. Krenning, et al. “Lutetium-labelled peptides for therapy of neuroendocrine tumours” Eur J Nucl Med Mol Imaging, vol. 39, pp. 103-112, 2012.
[10] A. Romer, D. Seiler, N. Marincek, et al. ”Somatostatin-based radiopeptide therapy with (177Lu-DOTA)-TOC versus (90Y-DOTA)-TOC in neuroendocrine tumours” Eur J Nucl Med Mol Imaging, vol. 41, pp. 214-222, 2014.
[11] M. Cremonesi, M. Ferrari, L. Bodei, et al. “Dosimetry in Peptide Radionuclide Receptor Therapy: A Review” J Nucl Med, vol. 47, pp. 1467-1475, 2006.
[12] J. A. Jacquez, Compartmental analysis in biology and medicine. Amsterdam, Holland: Elsevier/North, 1972.
[13] D. Anderson. Compartmental modeling and tracer kinetics. Springer-Verlag: Berlin, 1983.
[14] J. Robertson. Compartmental distribution of radiotracers. Boca Raton, FL: CRC Press, 1983.
[15] H. Yousefnia, M. Mousavi-Daramoroudi, S. Zolghadri and F. Abbasi-Davani, “Preparation and biodistribution assessment of low specific activity 177Lu-DOTATOC for optimization studies.” Iran J Nucl Med, vol. 24, pp. 85-91, 2016.
[16] P. E. Valk, D. L. Bailey, D. W. Townsend, M. N. Maisey, Positron Emission Tomography: Basic Science and Clinical Practice. Springer-Verlag: London, 2003, pp. 147–179.
[17] M. G. Stabin and J. A. Siegel, “Physical Models and Dose Factors for Use in Internal Dose Assessment.” Health Phys, vol. 85, pp. 294-310, 2003.
[18] M. G. Stabin, R.B. Sparks, E. Crowe, “OLINDA/EXM: the second-generation personal computer software for internal dose assessment in nuclear medicine.” J Nucl Med, vol. 46, pp. 1023–1027, 2005.
@article{"International Journal of Medical, Medicine and Health Sciences:77910", author = "S. Zolghadri and M. Mousavi-Daramoroudi and H. Yousefnia and F. Abbasi-Davani", title = "Absorbed Dose Estimation of 177Lu-DOTATOC in Adenocarcinoma Breast Cancer Bearing Mice", abstract = "In this study, the absorbed dose of human organs after injection of 177Lu-DOTATOC was studied based on the biodistribution of the complex in adenocarcinoma breast cancer bearing mice. For this purpose, the biodistribution of the radiolabelled complex was studied and compartmental modeling was applied to calculate the absorbed dose with high precision. As expected, 177Lu-DOTATOC illustrated a notable specific uptake in tumor and pancreas, organs with high level of somatostatin receptor on their surface and the effectiveness of the radio-conjugate for targeting of the breast adenocarcinoma tumors was indicated. The elicited results of modeling were the exponential equations, and those are utilized for obtaining the cumulated activity data by taking their integral. The results also exemplified that non-target absorbed-doses such as the liver, spleen and pancreas were approximately 0.008, 0.004, and 0.039, respectively. While these values were so much lower than target (tumor) absorbed-dose, it seems due to this low toxicity, this complex is a good agent for therapy.", keywords = "Breast cancer, compartmental modeling, 177Lu, dosimetry.", volume = "12", number = "9", pages = "383-5", }
